Extended follow-up of the German ARO 96-02 trial shows that adjuvant radiotherapy reduces the risk of biochemical failure in men whose prostate cancer extends through the prostate capsule (stage T3), compared with a wait-and-see approach, after radical prostatectomy. Adjuvant radiotherapy reduced the risk of biochemical failure (rising prostate-specific antigen [PSA] level) by 49% at 10 years in this study. The study was not powered to detect differences in overall survival, explained presenting author Thomas Wiegel, MD, University of Ulm, Germany, at the Genitourinary Cancers Symposium held recently in Orlando, Florida.1

“Our long-term follow-up shows that it is incorrect to say that adjuvant radiation for patients with positive surgical margins stage is overtreatment. It is clear that adjuvant radiotherapy reduces biochemical evidence of disease after 10 years. It is quite important that we had a low rate of side effects, with only one case of grade 3 late toxicity,” he stated.

Study Design

The study randomly assigned 385 men with stage T3 prostate cancer following radical prostatectomy in a 1:1 ratio to adjuvant radiotherapy vs a wait-and-see approach. Patients were randomized before they had an undetectable PSA level (< .05 ng/mL). The median number of positive nodes was eight; median follow-up was 112 months.

A total of 45 patients in the adjuvant radiotherapy arm and 33 in the wait-and-see arm failed to achieve an undetectable PSA level and were excluded from the analysis as planned. Another 34 patients in the adjuvant radiotherapy arm refused treatment. The intent-to-treat analysis was based on 148 patients in the adjuvant radiotherapy arm and 159 in the wait-and-see arm.

All patients had stage T3 disease; 27% had T3c (extension of cancer to the seminal vesicles). The majority of patients had Gleason scores ranging from 7 to 9.

Major Findings

At 10 years, freedom from biochemical failure was achieved in 56% of the adjuvant radiotherapy arm vs 35% of the wait-and-see arm, for an absolute difference of 21% favoring adjuvant treatment (P = .00002). No significant benefit was observed for adjuvant radiotherapy regarding metastasis-free survival or overall survival, although the trial was not powered to show this.

For patients with positive surgical margins, adjuvant radiotherapy had a clear advantage: Biochemical control was achieved in 55% vs 27% of those in the wait-and-see arm, for an absolute difference of 28%.

The rate of late side effects from radiation was quite low, especially compared to two similar previous trials conducted by the Southwest Oncology Group (SWOG)2 and the European Organisation for Research and Treatment of Cancer (EORTC).3

Dr. Wiegel said that in the SWOG trial, adjuvant radiotherapy not only reduced the rate of biochemical failure but also improved metastasis-free and overall survival at 12 years. The EORTC trial showed a 20% improvement in biochemical failure but no survival ­advantage.

“Our trial is the only clear adjuvant trial, because it is the only trial where patients had an undetectable PSA before receiving radiotherapy,” Dr. Wiegel stated. ■

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Now there are mature data from three trials comparing adjuvant radiotherapy vs a wait-and see approach in men following radical prostatectomy, said formal discussant Anthony D’Amico, MD, Dana-Farber Cancer Center and Harvard Medical School, Boston, at the Genitourinary Cancers Symposium.